chr16-89710700-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004913.3(VPS9D1):​c.1144G>T​(p.Asp382Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000622 in 1,608,802 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

VPS9D1
NM_004913.3 missense

Scores

4
13
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94
Variant links:
Genes affected
VPS9D1 (HGNC:13526): (VPS9 domain containing 1) Enables identical protein binding activity. Predicted to be involved in ATP synthesis coupled proton transport. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VPS9D1NM_004913.3 linkuse as main transcriptc.1144G>T p.Asp382Tyr missense_variant 10/15 ENST00000389386.8 NP_004904.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
VPS9D1ENST00000389386.8 linkuse as main transcriptc.1144G>T p.Asp382Tyr missense_variant 10/151 NM_004913.3 ENSP00000374037 A2Q9Y2B5-1
VPS9D1ENST00000561976.5 linkuse as main transcriptc.934G>T p.Asp312Tyr missense_variant 9/141 ENSP00000454244 P2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152198
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000170
AC:
4
AN:
235236
Hom.:
0
AF XY:
0.0000233
AC XY:
3
AN XY:
128816
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000173
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000946
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000549
AC:
8
AN:
1456486
Hom.:
0
Cov.:
32
AF XY:
0.00000690
AC XY:
5
AN XY:
724202
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152316
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ExAC
AF:
0.00000829
AC:
1
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 01, 2021The c.1144G>T (p.D382Y) alteration is located in exon 10 (coding exon 10) of the VPS9D1 gene. This alteration results from a G to T substitution at nucleotide position 1144, causing the aspartic acid (D) at amino acid position 382 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.62
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Pathogenic
0.14
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.37
.;T
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Pathogenic
0.34
D
MetaRNN
Uncertain
0.50
T;T
MetaSVM
Uncertain
-0.28
T
MutationAssessor
Uncertain
2.5
.;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.74
T
PROVEAN
Uncertain
-3.4
D;D
REVEL
Uncertain
0.33
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.0030
D;D
Polyphen
1.0
.;D
Vest4
0.80
MVP
0.32
MPC
0.80
ClinPred
0.97
D
GERP RS
4.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.71
gMVP
0.78

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200129122; hg19: chr16-89777108; API